Small molecule obefazimod shows promise in UC

In the open-label extension of a phase 2b induction trial of obefazimod in ulcerative colitis (UC), more than half of the patients gained clinical remission and about one-third endoscopic remission at week 48. Among the patients in clinical remission at this point, 48.2% had not yet achieved remission when entering the maintenance trial.

Obefazimod is a small molecule, entailing an upregulation of microRNA 124 and a consequent decrease in inflammatory cytokines and chemokines [1,2]. After positive results of a 16-week induction trial (NCT04023396) that assessed various treatment regimens in adult patients with moderate-to severe UC, all participants were eligible to enter a 96-week, open-label extension [1]. In terms of a first evaluation of long-term efficacy and safety of once-daily 50 mg obefazimod, the 48-week interim data was presented.

Of the participants in the initial study cohort, 97.7% (n=217) took part in the open-label extension trial. The participants had a mean age of 42.1 years, were predominantly men, and had a median faecal calprotectin level of 204.7 µg/g. Nearly half used corticosteroids and 45.2% had been treated with biologics or JAK inhibitors before. For those who did not complete week 48, non-responder imputation was used.

At week 48, the rates of clinical remission and clinical response were 54.8% and 82.0%. The proportion of patients within these groups who experienced these outcomes de novo, meaning they had no remission or response after induction, were 48.2% and 76.3%. Endoscopic improvement was present in 61.3% of patients and endoscopic remission was achieved by 33.2%. Of these 2 outcomes, there were de novo rates of 54.6% and 30.3%, respectively. Overall, 124/217 participants in the extension cohort had a response after 8 weeks of induction. Of these primary responders, 66.1% were in clinical remission, 37.9% in endoscopic remission, and 70.2% demonstrated endoscopic improvement at week 48.

The safety analysis found 65% of participants with ≥1 treatment-emergent adverse event (TEAE), with serious TEAEs in 7.8%. The study had to be discontinued due to TEAEs in 6.9% of participants. Most frequent were COVID-19 and headache (both in 11.5%), as well as UC and nasopharyngitis (in 6.9% and 6.5%).

In conclusion, Prof. Séverine Vermeire (University Hospital Leuven, Belgium) and co-authors confirmed a long-term efficacy and a favourable safety profile of obefazimod at a dosage of 50 mg/day in this phase 2b trial. A global phase 3 induction and maintenance study will be initiated soon.

1. Vermeire S, et al. ABX464 (obefazimod) in patients with moderate-to-severe ulcerative colitis: an interim 48-week safety and efficacy analysis from an ongoing 96-week open-label maintenance phase 2b study. MP250, UEG Week 2022, 8–11 October, Vienna, Austria.
2. Vermeire S, et al. Lancet Gastroenterol Hepatol. 2022;7(11):1024–1035.

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Posted on 1 December, 20228 April, 2024